An injectable chitosan/chondroitin sulfate hydrogel with tunable mechanical properties for cell therapy/tissue engineering

Chitosan (CH) hydrogels with remarkable mechanical properties and rapid gelation rate were recently synthesized by combining sodium hydrogen carbonate (SHC) with another weak base, such as beta-glycerophosphate (BGP). To improve their biological responses, in the present study, chondroitin sulfate (CS) was added to these CH hydrogels. Hydrogel characteristics in terms of pH and osmolarity, as well as rheological, mechanical, morphological and swelling properties, were studied in the absence and presence of CS. Effect of CS addition on cytocompatibility of hydrogels was also assessed by evaluating the viability and metabolic activity of encapsulated L929 fibroblasts. New CH hydrogels containing CS were thermosensitive and injectable with pH and osmolality close to physiological levels and enhanced swelling capacity. Encapsulated cells were able to maintain their viability and proliferative capacity up to 7 days and CS addition improved the viability of the cells, particularly in serum-free conditions. Addition of CS showed a reducing and dose-dependent effect on the mechanical strength of the hydrogels after complete gelation. This work provides evidence that CH-CS hydrogels prepared with a combination of SHC and BGP as a gelling agent have a promising potential to be used as thermosensitive, injectable and biocompatible matrices with tunable mechanical properties for cell therapy applications.